Mechanism of cell fate choice between neural and mesodermal development during early embryogenesis

Cell lineage determination during early embryogenesis has profound effects on adult animal development. Pre-patterning of embryos, such as that of Drosophila and Caenorhabditis elegans, is driven by asymmetrically localized maternal or zygotic factors, including mRNA species and RNA binding proteins. However, it is not clear how mammalian early embryogenesis is regulated and what the early cell fate determinants are. Here we show that, in mouse, mitochondrial ribosomal RNAs (mtrRNAs) are differentially distributed between 2-cell sister blastomeres. This distribution pattern is not related to the overall quantity or activity of mitochondria which appears equal between 2-cell sister blastomeres. Like in lower species, 16S mtrRNA is found to localize in the cytoplasm outside of mitochondria in mouse 2-cell embryos. Alterations of 16S mtrRNA levels in one of the 2-cell sister blastomere via microinjection of either sense or anti-sense RNAs drive its progeny into different cell lineages in blastocyst. These results indicate that mtrRNAs are differentially distributed among embryonic cells at the beginning of embryogenesis in mouse and they are functionally involved in the regulation of cell lineage allocations in blastocyst, suggesting an underlying molecular mechanism that regulates pre-implantation embryogenesis in mouse.

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AtNSE1 and AtNSE3 are required for embryo pattern formation and maintenance of cell viability during Arabidopsis embryogenesis

Journal of Experimental Botany ◽

10.1093/jxb/erz373 ◽

2019 ◽

Vol 70 (21) ◽

pp. 6229-6244

Author(s):

Gang Li ◽

Wenxuan Zou ◽

Liufang Jian ◽

Jie Qian ◽

Jie Zhao

Keyword(s):

Cell Death ◽

Cell Viability ◽

Cell Fate ◽

Embryo Development ◽

Higher Plants ◽

Early Embryo ◽

Embryo Cell ◽

Early Embryogenesis ◽

Embryo Abortion ◽

Cell Fate Decisions

Abstract Embryogenesis is an essential process during seed development in higher plants. It has previously been shown that mutation of the Arabidopsis non-SMC element genes AtNSE1 or AtNSE3 leads to early embryo abortion, and their proteins can interact with each other directly. However, the crucial regions of these proteins in this interaction and how the proteins are cytologically involved in Arabidopsis embryo development are unknown. In this study, we found that the C-terminal including the Ring-like motif of AtNSE1 can interact with the N-terminal of AtNSE3, and only the Ring-like motif is essential for binding with three α motifs of AtNSE2 (homologous to AtMMS21). Using genetic assays and by analysing molecular markers of cell fate decisions (STM, WOX5, and WOX8) in mutant nse1 and nse3 embryos, we found that AtNSE1 and AtNSE3 work non-redundantly in early embryo development, and that differentiation of the apical meristem and the hypophysis fails in the mutants, which have disrupted auxin transportation and responses. However, the upper cells of the suspensor in the mutants seem to have proper embryo cell identity. Cytological examination showed that cell death occurred from the early embryo stage, and that vacuolar programmed cell death and necrosis in the nse1 and nse3 mutant embryos led to ovule abortion. Thus, AtNSE1 and AtNSE3 are essential for maintaining cell viability and growth during early embryogenesis. Our results improve our understanding of the functions of SMC5/6 complex in early embryogenesis in Arabidopsis.

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Zebrafish Polycomb repressive complex-2 critical roles are largely Ezh2- over Ezh1-driven and concentrate during early embryogenesis

10.1101/2020.12.31.424918 ◽

2021 ◽

Author(s):

Gabriel A. Yette ◽

Scott Stewart ◽

Kryn Stankunas

Keyword(s):

Cell Fate ◽

Transcriptional Repression ◽

Axial Skeleton ◽

Early Embryogenesis ◽

Loss Of Function ◽

Allelic Series ◽

Polycomb Repressive Complex ◽

Genetic Studies ◽

Polycomb Repressive Complex 2 ◽

Early Developmental

ABSTRACTPolycomb repressive complex-2 (PRC2) methylation of histone H3 lysine-27 (H3K27me) is associated with stable transcriptional repression. PRC2 famously silences Hox genes to maintain anterior-posterior segment identities but also enables early cell fate specification, restrains progenitor cell differentiation, and canalizes cell identities. Zebrafish PRC2 genetic studies have focused on ezh2, which, with its paralog ezh1, encodes the H3K27 methyltransferase component. ezh2 loss-of-function mutants reinforce essential vertebrate PRC2 functions during early embryogenesis albeit with limited contributions to body plan establishment. However, redundancy with ezh1 and the lethality of maternal-zygotic homozygous ezh2 nulls could obscure additional early developmental and organogenesis roles of PRC2. Here, we combine new and existing zebrafish ezh1 and ezh2 alleles to show collective maternal/zygotic ezh2 exclusively provides earliest embryonic PRC2 H3K27me3 activity. Zygotic ezh1, which becomes progressively expressed as ezh2 levels dissipate, has minor redundant and noncompensatory larval roles but itself is not required for viability or fertility. Zygotic Ezh2/PRC2 promotes correct craniofacial bone shape and size by maintaining proliferative pre-osteoblast pools. An ezh2 allelic series including disrupted maternal ezh2 uncovers axial skeleton homeotic transformations and pleiotropic organogenesis defects. Further, once past a critical early window, we show zebrafish can develop near normally with minimal bulk H3K27me3. Our results suggest Ezh2-containing PRC2 stabilizes rather than instructs early developmental decisions while broadly contributing to organ size and embellishment.

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Lineage commitment of embryonic cells involves MEK1-dependent clearance of pluripotency regulator Ventx2

eLife ◽

10.7554/elife.21526 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 2

Author(s):

Pierluigi Scerbo ◽

Leslie Marchal ◽

Laurent Kodjabachian

Keyword(s):

Cell Division ◽

Cell Fate ◽

Early Embryogenesis ◽

Embryonic Cells ◽

Pluripotent Cells ◽

Embryonic Tissues ◽

Pluripotency Gene ◽

Related Transcription Factor ◽

Over Time

During early embryogenesis, cells must exit pluripotency and commit to multiple lineages in all germ-layers. How this transition is operated in vivo is poorly understood. Here, we report that MEK1 and the Nanog-related transcription factor Ventx2 coordinate this transition. MEK1 was required to make Xenopus pluripotent cells competent to respond to all cell fate inducers tested. Importantly, MEK1 activity was necessary to clear the pluripotency protein Ventx2 at the onset of gastrulation. Thus, concomitant MEK1 and Ventx2 knockdown restored the competence of embryonic cells to differentiate. Strikingly, MEK1 appeared to control the asymmetric inheritance of Ventx2 protein following cell division. Consistently, when Ventx2 lacked a functional PEST-destruction motif, it was stabilized, displayed symmetric distribution during cell division and could efficiently maintain pluripotency gene expression over time. We suggest that asymmetric clearance of pluripotency regulators may represent an important mechanism to ensure the progressive assembly of primitive embryonic tissues.

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Chromatin Regulation in Development: Current Understanding and Approaches

Stem Cells International ◽

10.1155/2021/8817581 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Zi Hao Zheng ◽

Tsz Wing Sam ◽

YingYing Zeng ◽

Justin Jang Hann Chu ◽

Yuin-Han Loh

Keyword(s):

Cell Fate ◽

Regulatory Elements ◽

Histone Variants ◽

Early Embryogenesis ◽

Gene Interactions ◽

Cell Fate Determination ◽

Chromatin Regulation ◽

Cell Fates ◽

Stem Cell Fate

The regulation of mammalian stem cell fate during differentiation is complex and can be delineated across many levels. At the chromatin level, the replacement of histone variants by chromatin-modifying proteins, enrichment of specific active and repressive histone modifications, long-range gene interactions, and topological changes all play crucial roles in the determination of cell fate. These processes control regulatory elements of critical transcriptional factors, thereby establishing the networks unique to different cell fates and initiate waves of distinctive transcription events. Due to the technical challenges posed by previous methods, it was difficult to decipher the mechanism of cell fate determination at early embryogenesis through chromatin regulation. Recently, single-cell approaches have revolutionised the field of developmental biology, allowing unprecedented insights into chromatin structure and interactions in early lineage segregation events during differentiation. Here, we review the recent technological advancements and how they have furthered our understanding of chromatin regulation during early differentiation events.

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The suspensor as a model system to study the mechanism of cell fate specification during early embryogenesis

Plant Reproduction ◽

10.1007/s00497-018-0326-5 ◽

2018 ◽

Vol 31 (1) ◽

pp. 59-65 ◽

Cited By ~ 9

Author(s):

Xiongbo Peng ◽

Meng-Xiang Sun

Keyword(s):

Cell Fate ◽

Model System ◽

Early Embryogenesis ◽

Cell Fate Specification ◽

Fate Specification

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The conserved AAA-ATPase PCH-2 TRIP13 regulates spindle checkpoint strength

Molecular Biology of the Cell ◽

10.1091/mbc.e20-05-0310 ◽

2020 ◽

Vol 31 (20) ◽

pp. 2219-2233

Author(s):

Lénaïg Défachelles ◽

Anna E. Russo ◽

Christian R. Nelson ◽

Needhi Bhalla

Keyword(s):

Cell Cycle ◽

Cell Volume ◽

Cell Fate ◽

Spindle Checkpoint ◽

Early Embryogenesis ◽

Aaa Atpase ◽

Cell Cycle Delay ◽

C Elegans

The length of the cell cycle delay imposed by the spindle checkpoint, also referred to as the spindle checkpoint strength, is controlled by the number of unattached kinetochores, cell volume, and cell fate. We show that PCH-2, a highly conserved AAA-ATPase, controls checkpoint strength during early embryogenesis in C. elegans.

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Accessible chromatin reveals regulatory mechanisms underlying cell fate decisions during early embryogenesis

Scientific Reports ◽

10.1038/s41598-021-86919-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tongqiang Fan ◽

Youjun Huang

Keyword(s):

Cell Fate ◽

Chromatin Accessibility ◽

Early Embryogenesis ◽

Regulatory Sequences ◽

Cell Fate Decision ◽

Joint Research ◽

Cell Fate Decisions ◽

Fate Decision ◽

Multiple Species ◽

Accessible Chromatin

AbstractThis study was conducted to investigate epigenetic landscape across multiple species and identify transcription factors (TFs) and their roles in controlling cell fate decision events during early embryogenesis. We made a comprehensively joint-research of chromatin accessibility of five species during embryogenesis by integration of ATAC-seq and RNA-seq datasets. Regulatory roles of candidate early embryonic TFs were investigated. Widespread accessible chromatin in early embryos overlapped with putative cis-regulatory sequences. Sets of cell-fate-determining TFs were identified. YOX1, a key cell cycle regulator, were found to homologous to clusters of TFs that are involved in neuron and epidermal cell-fate determination. Our research provides an intriguing insight into evolution of cell-fate decision during early embryogenesis among organisms.

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Ectopic POU5F1 in the male germ lineage disrupts differentiation and spermatogenesis in mice

Reproduction ◽

10.1530/rep-16-0140 ◽

2016 ◽

Vol 152 (4) ◽

pp. 363-377 ◽

Cited By ~ 2

Author(s):

Yu Zheng ◽

LeAnna J Phillips ◽

Rachel Hartman ◽

Junhui An ◽

Christina T Dann

Keyword(s):

Stem Cell ◽

Cell Fate ◽

Germ Cells ◽

Progenitor Cell ◽

Ectopic Expression ◽

Transgenic Mouse Model ◽

Spermatogonial Stem Cell ◽

Early Embryogenesis ◽

Cell Lineages ◽

Progenitor Cell Population

Expression levels of the pluripotency determinant, POU5F1, are tightly regulated to ensure appropriate differentiation during early embryogenesis. POU5F1 is also present in the spermatogonial stem cell/progenitor cell population in mice and it is downregulated as spermatogenesis progresses. To test if POU5F1 downregulation is required for SSCs to differentiate, we produced transgenic mice that ubiquitously express POU5F1 in Cre-expressing lineages. Using a Vasa-Cre driver to produce ectopic POU5F1 in all postnatal germ cells, we found that POU5F1 downregulation was necessary for spermatogonial expansion during the first wave of spermatogenesis and for the production of differentiated spermatogonia capable of undergoing meiosis. In contrast, undifferentiated spermatogonia were maintained throughout adulthood, consistent with a normal presence of POU5F1 in these cells. The results suggest that POU5F1 downregulation in differentiating spermatogonia is a necessary step for the progression of spermatogenesis. Further, the creation of a transgenic mouse model for conditional ectopic expression of POU5F1 may be a useful resource for studies of POU5F1 in other cell lineages, during tumorogenesis and cell fate reprogramming.

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The interplay of HSP90s with YDA regulates main body axis formation during early embryogenesis in Arabidopsis

10.1101/2020.09.29.319384 ◽

2020 ◽

Author(s):

Despina Samakovli ◽

Tereza Tichá ◽

Tereza Vavrdová ◽

Natálie Závorková ◽

Ales Pecinka ◽

...

Keyword(s):

Cell Fate ◽

Embryo Development ◽

Early Embryo ◽

Early Embryogenesis ◽

Transcriptional Networks ◽

Axis Formation ◽

Main Body ◽

Epigenetic Control ◽

Auxin Distribution ◽

Shock Proteins

AbstractThe YODA kinase (YDA) pathway is intimately associated with the control of Arabidopsis thaliana embryo development but little is known regarding its regulators. Using genetic analysis, HEAT SHOCK PROTEINS 90 (HSP90s) emerge as potent regulators of YDA in the process of embryo development and patterning. This study is focused on the characterization and quantification of early embryonal traits of single and double hsp90 and yda mutants. The mutant analysis was supported by expression analyses of cell-specific WUSCHEL-RELATED HOMEOBOX 2 (WOX2) and WOX8 genes during early embryonic development. Chromatin immunoprecipitation assays corroborated the involvement of YDA and HSP90s in the epigenetic control of chromatin remodeling during early embryogenesis. Genetic interactions among HSP90s and members of the YDA signaling pathway affected the development of both embryo proper and suspensor. Impaired function of HSP90s or YDA had an impact on the spatiotemporal expression of WOX8 and WOX2 suggesting their essential role in cell fate determination and interference with auxin distribution. Hence, the interplay between HSP90s and YDA signaling cascade mediates the epigenetic control regulating the transcriptional networks shaping early embryo development.

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